This research project continues our effort towards elucidation of theoretical and therapeutic aspects of three principal disorders of calcification, -postmenopausal osteoporosis, hyperparathyroidism, and osteomalacia. The ultimate goal is the elucidation of underlying pathogenetic mechanisms, and application of this knowledge toward development of improved diagnostic approach and rational treatment program. Well-established techniques and approaches developed in an earlier successful study of hypercalciuria will be applied in this study of bone diseases. The first objective will test the hypothesis that postmenopausal osteoporosis is multifactorial in etiology, and that thiazide and/or 25-hydroxyvitamin D may have a therapeutic role. The second objective assumes that primary hyperparathyroidism may be classified on the basis of physiological derangements, that these derangements may be utilized to define indications for parathyroid surgery, and that there may be a vitamine D-independent component for the increased calcium absorption. The final objective addressed the hypotheses that 25-hydroxyvitamine D, 24,25-dihydroxyvitamine D and 1,25-dihydroxyvitamin D each possess intrinsic biologic activity, that their actions are different qualitatively and quantitatively, and that osteomalacia may result from specific abnormalities in the metabolism or in the responsiveness to these various metabolites. Structure function relationships will be sought by examination of intestinal receptors for 1,25-dihydroxyvitamin D in disorders of vitamin D metabolism.